The association of the lac repressor with its operator is the best understood example of a specific protein-DNA recognition process. Our studies have been directed towards providing a dynamic picture of the events which transpire as this protein binds to DNA. We have attached fluorescent probes to the repressor, both covalently and noncovalently. These probes have revealed that the lac repressor undergoes several conformational changes as it associates with the nonoperator DNA, poly(d(A-T)). The rapid kinetics of these changes have been monitored using stopped-flow techniques. We will expand these studies to include the association of the repressor with its operator. By comparing the conformational changes within the repressor as it binds to both operator and nonoperator DNA, we hope to reveal differences which are responsible for the selectivity of this protein for its operator. We will also carry out stopped-flow fluorescence polarization studies to determine if these conformational changes occur before or after the repressor binds to poly(d(A-T)). The stoichiometry of repressor-poly(d(A-T)) binding, as monitored by these fluorescent probes, differs at low and high ionic strengths. Circular dichroism titrations will be carried out to explore these differences.